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K Shioda

Publications and source records attributed to K Shioda.

At least 19 recordsLinked to original sources
PubMed2004

Memantine, an NMDA antagonist, prevents the development of hyperthermia in an animal model for serotonin syndrome.

BACKGROUND: Serotonin (5-HT) syndrome is the most serious side effect of antidepressants. Although several drugs have been used for the treatment of 5-HT syndrome, a universal pharmacotherapy has not been established. NMDA receptor antagonists have been reported to have neuroprotective effects. In the present study, the efficacy of NMDA antagonists, including memantine and MK-801, and potent 5-HT (2A) antagonists, including risperidone and ketanserin, was evaluated in a 5-HT syndrome animal model. METHODS: 5-Hydroxy-l-tryptophan (100 mg/kg) and clorgyline (2 mg/kg) were administered intraperitoneally in rats to induce 5-HT syndrome. The rectal temperature of the rats was measured, and the noradrenaline (NA) and 5-HT levels in the anterior hypothalamus were measured using a microdialysis technique. RESULTS: In the group pretreated with saline, the rectal temperature increased to more than 40 degrees C, and all of the animals died within 90 min of the drug's administration. The NA and 5-HT levels in the anterior hypothalamus increased to about 15- and 1100-fold of the pre-administration levels, respectively. Pretreatment with risperidone (0.5 mg/kg) and ketanserin (5 mg/kg) prevented the development of hyperthermia and the increase in the NA level. Memantine (10 mg/kg) and MK-801 (0.5 mg/kg) also prevented the development of hyperthermia and the increase in the NA level. These results suggest that NMDA antagonists, as well as potent 5-HT (2A) antagonists, may be effective drugs for the treatment of 5-HT syndrome. CONCLUSIONS: Since memantine is clinically well tolerated, this drug is a particularly promising therapeutic drug for 5-HT syndrome treatment.

5-Hydroxytryptophan↗
PubMed2001

Oxidative stress and disturbed glutamate transport in hereditary nucleotide repair disorders.

Xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are hereditary DNA repair disorders complicated by progressive neurodegeneration. Here we immunohistochemically examine the in situ expression of materials that are produced by oxidative stress and glutamate transporters (which can contribute to prevention of glutamate neurotoxicity) in the brains of 5 autopsied patients each of XPA, CS, and control groups. All oxidative products, including nitrotyrosine, advanced glycation end product, and 4-hydroxy-2-nonenal-modified protein (HNE) were deposited in large amounts in the globus pallidus of CS patients compared to XPA patients. They were frequently recognized in the pseudocalcified foci and free minerals in the neuropil, and more rarely in foamy spheroids. In addition, the deposition of HNE was observed also in hippocampal and cerebellar dentate neurons of both CS and XPA patients. The expression of glial glutamate transporters, EAAT1 and GLT-1, was affected in the globus pallidus in 5 CS patients and 3 XPA patients. They were also altered in the cerebellar cortex in most of the CS patients. These data suggest that oxidative stress and disturbed glutamate transport may be involved in pallidal and/or cerebellar degeneration in hereditary nucleotide repair disorders.

ATP-Binding Cassette Transporters↗
PubMed2001

[A case of myeloma kidney complicated by extramedullary plasmacytoma with massive bleeding].

A 76-year-old woman, who had received hemodialysis due to chronic renal failure of unknown cause for two months, was admitted to our hospital. She was suffering from severe pain in the left thigh, rapidly progressive anemia and thrombocytopenia after receiving a contusion on her left thigh. Soon after admission, the patient died of shock. Autopsy revealed multiple myeloma(lamda type) with extramedullary plasmacytoma and systemic amyloidosis. In the kidney, there were typical tubular casts with multinucleated giant cells and interstitial fibrosis. More specific findings included an extramedullary plasmacytoma in the left iliopsoas muscle surrounded by a huge hematoma. Internal hemorrhage resulting from indirect contusion at this site was likely to have caused her shock. Since typical clinical findings of multiple myeloma, such as serum M protein and hypercalcemia, were not found in this case, it was difficult to make a diagnosis of multiple myeloma. In case of multiple myeloma, micro- or macroscopic extramedullary tumor formation is not rare, but there has been no report of a case with macroscopic tumor formed in skeletal muscle, exhibiting massive hemorrhage. We report here a case of multiple myeloma with an unusual clinical course.

Aged↗
PubMed1999

Neurodegeneration in hereditary nucleotide repair disorders.

Both xeroderma pigmentosum group A (XPA) and Cockayne syndrome (CS) are rare autosomal disorders, have a genetic defect in the step of nucleotide repair, and involve various neurological abnormalities caused by progressive neurodegeneration. We performed comprehensive neuropathological analysis of five cases of XPA and four cases of CS. The XPA cases showed widespread neuronal loss throughout the central nervous system, in sharp contrast to the comparative preservation of neurons in the CS cases, who rather exhibited patchy demyelination in the cerebral and cerebellar white matter, and multifocal calcium deposition in the basal ganglia and cerebral white matter, respectively. Exceptionally in the cerebellar cortex, neuronal loss was more severe in CS than in XPA. Grumose or foamy spheroid bodies occurred in the globus pallidus and substantia nigra, and axonal torpedoes were increased in the cerebellar cortex in both disorders. Neither silver impregnation nor immunohistochemistry for ubiquitin or tau succeeded in visualizing neurofibrillary tangles, senile plaques or augmented ubiquitination in either disorder, and these findings did not support the involvement of facilitated aging in the neurodegeneration in XPA or CS.

Adolescent↗
PubMed1998

Cerebellar neurodegeneration in human hereditary DNA repair disorders.

Recent findings have focused attention on the role of apoptosis in neurodegenerative diseases, however, the apoptotic process in child-onset brain disorders has been little investigated. Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are hereditary disorders characterized by impaired DNA repair and neurodegeneration. We investigated apoptotic cell death in the cerebellum of five cases of XP group A (XPA), four cases of CS, and twelve controls, using TdT-mediated DIG-dUTP nick-end labeling (TUNEL) and immunohistochemical staining for bcl-2, bcl-x, p53, bax, BDNF and Trk B. The TUNEL-positive cells were found in the granule cells of the cerebellar cortex of two patients with XPA and two patients with CS, whereas such cells were not detected in the cerebellar cortex in controls. Upregulation of bcl-2 or BDNF was not observed, and bcl-x expression was not altered. Some patients showed nuclear expression of p53 in the granule cells and/or molecular layer, bax-positive glial cells in the cerebellar white matter, and a few Trk B-positive cells in the granular layer. These findings suggest that apoptotic cell death can be involved in the cerebellar degeneration in patients with hereditary defects in DNA repair mechanisms.

Adolescent↗
PubMed1997

[Female autopsy case of Seitelberger's connatal form of Pelizaeus-Merzbacher disease].

We report here an autopsy case of connatal Pelizaeus-Merzbacher disease, the second from Japan. Her clinico-pathological findings were essentially the same as those of the first case that we reported previously. The clinical course of this patient was 19 years in duration. Pathologically myelin had disappeared from the entire central nervous system, whereas that of the peripheral nervous system was preserved. Axons appeared also intact except for torpedo formation in the cerebellum. Demyelinated areas showed isomorphic gliosis. Recent studies have revealed impairment of proteolipid protein synthesis in classical Pelizaeus-Merzbacher disease, the causative gene of which being located on the X chromosome. Thus, this disease is inherited as an X-linked recessive trait. However we report herein a sporadic female case in a non-consanguineous family. Therefore, we propose that this disease might have another causative gene and/or another mode of inheritance.

Adult↗
PubMed1995

[Yolk sac tumor resected by transverse sternotomy: a case report].

Transverse sternotomy was performed in a 39-year-old man having bilateral lung metastatic lesions of yolk sac tumor. This approach provided an excellent operative field. Bilateral partial lobes including parietal pleura and diaphragma were readily resected. As described in this paper, transverse sternotomy is one of the beneficial method in the thorough surgical treatment for metastatic bilateral lung lesion.

Adult↗
PubMed1995

[An autopsy case of Down syndrome in an adult patient with multiple senile plaques and systemic amyloidosis].

A rare adult autopsy case of Down syndrome was reported. The patient was a 36-year-old male, whose chromosome analysis revealed 47, XY, +21. He showed typical systemic AA-amyloidosis and numerous senile plaques in the brain. Senile plaques were diffuse or primitive. They were composed of beta-protein, but negative for Congo-red stain. There were few neurofibrillary changes in the para hippocampal gyri. Nucleus basalis Meynert showed no significant lesion. The distribution of these plaques had some characteristics different from that for Alzheimer's disease. In the brain involvement of systemic AA-amyloidosis was restricted to the regions devoid of blood-brain-barrier, such as choroid plexus and pituitary gland. Cerebral beta-amyloid and systemic amyloid A protein were segregated on each side of the blood-brain-barrier. Therefore, we suggested that each amyloid might be synthesized and deposited by its own mechanism. Electronmicroscopically Hirano's body was identified in the hippocampal gyri.

Adult↗
PubMed1994

Deoxyuridine triphosphatase in human hepatoma.

1. Deoxyuridine triphosphatase (dUTPase) in human hepatoma was investigated. The apparent activity in a gram weight tissue was about 6 times that of the activity in rat livers after partial hepatectomy. 2. Most catalytic properties of the hepatoma dUTPase were similar to the enzymes from other sources. 3. The hepatoma dUTPase reacted with the antibodies against the rat spleen dUTPase, although the molecular size of the enzyme (46-48 kDa) was different to the rat enzyme. 4. The immunochemical studies indicated that the enzyme was composed of two identical subunits, whose molecular mass was about 22 kDa.

Animals↗
PubMed1993

The pathogenesis of biliary atresia: a morphological study of the hepatobiliary system and the hepatic artery.

Specimens of the extrahepatic biliary trees and wedge liver biopsies were studied in 11 cases of biliary atresia. The hepatic arteries at the porta hepatis were examined with ultrasound in five of the 11 cases. The basic histopathological features were found to be epithelial damage and an inflammatory, sclerosing change of both the intrahepatic and the extrahepatic biliary trees, combined with an arteriopathy manifesting as hyperplasia and hypertrophy of the hepatic arteries in all cases. Based on the results of ultrasonography and histological examination, this arteriopathy was thought to affect the arteries from the trunk of the common hepatic artery to its peripheral branches supplying the entire biliary tree. To determine whether these morphologically abnormal hepatic arteries are related to the pathogenesis of biliary atresia in association with abnormal blood flow and pressure requires further investigation.

Biliary Atresia↗
PubMed1992

Immunohistochemical studies on the new type of astrocytic inclusions identified in a patient with brain malformation.

Immunohistochemical studies were carried out on the new type of cerebral cortical astrocytic inclusions recently discovered in a 20-year-old patient with maldeveloped brain and micropolygyria. The inclusions appeared as eosinophilic structures (hematoxylin and eosin stain) and did not exhibit argyrophilia (modified Bielschowsky method). The inclusions were strongly stained by the antibody against S-100 protein (S 100) and to a lesser extent by the antibody to microtubule-associated protein 1B (MAP 1B). In contrast to Rosenthal fibers, the astrocytic inclusions did not react with antibodies to alpha B-crystallin, glial fibrillary acidic protein and ubiquitin. No positive reactions were obtained with antibodies against heat-shock protein 27 (HSP 27), HSP 72, actin, vimentin, desmin, cytokeratin, myelin basic protein, beta-tubulin, MAP 2, tau protein, paired helical filament, phosphorylated neurofilament protein (NFP), nonphosphorylated NFP, synaptophysin, cathepsin D, alpha 1-antichymotrypsin, alpha 1-antitrypsin and basic fibroblast growth factor. By immunoelectron microscopy, the products of the reaction with the anti-S 100 antibody appeared as heterogeneous granular deposits and with the antibody to MAP 1B they were randomly scattered throughout the astrocytic inclusions. Our results demonstrate that the immunohistochemical profile of the recently described inclusions differs from that of Rosenthal fibers. Whether the novel inclusions are involved in congenital astrocyte dysfunction and cerebral malformation remains to be established.

Adult↗
PubMed1992

Inclusion bodies in cerebral cortical astrocytes: a new change of astrocytes.

A unique pathological finding of astrocytes was observed in the brain of a 20-year-old man who had severe physical and mental retardation. The brain was malformed showing micropolygyria in several cortical areas. A large number of hypertrophic astrocytes with eosinophilic granular substances in their cytoplasm were found throughout the cerebral cortex. Several staining procedures and electron microscopical examinations were carried out on these intracytoplasmic inclusion. It was found that the appearance and staining character of these inclusions were different from other astrocytic changes, especially the Rosenthal fiber, described so far. The authors consider that these inclusion bodies in cerebral cortical astrocytes represent new pathological changes of astrocytes that appear to be associated with malformation of the brain.

Adult↗